Syphilis is a chronic, multistage infection caused by the spirochete Treponema pallidum subsp. pallidum and still represents a major health problem in the United States and worldwide. Inability to culture T. pallidum in vitro has hampered the study of factors involved in host-pathogen interactions. A global analysis of important T. pallidum antigens would be an important step forward in understanding the immune response to infection, and may lead to the identification of proteins useful in immunodiagnosis of syphilis or, potentially, prevention of infection through vaccination. [unreadable] In previous studies, a global screening of 908 T. pallidum gene products in a protein array identified a subset of proteins that are highly reactive with serum from syphilis patients and T. pallidum-infected rabbits. The purpose of the proposed studies is to determine the importance of these antigens in the immune response against T. pallidum infection and in host-pathogen interactions. In Specific Aim 1, the reactivity of newly identified, highly reactive T. pallidum antigens with a panel of sera from human syphilis patients, and hence their importance in the immune response and potential use in immunodiagnosis, will be determined. In Specific Aim 2, we will assess the importance of these novel T. pallidum antigens in host-pathogen interactions by determining immunoprotection in the rabbit model and cellular location and binding properties of the antigens. [unreadable] In summary, syphilis is a sexually transmitted disease that, despite the availability of effective therapy, has a major medical, economic, and social impact both in the United States and other countries. The public health benefit of this project will be the identification of antigens that may improve the diagnosis of syphilis and may lead to the development of an effective vaccine against the disease. [unreadable] [unreadable] [unreadable] [unreadable]